The long term objectives of this project are to understand the immunological and virological factors involved in the pathogenesis of HIV-1 infection. The information will be useful in the development of an effective vaccine for prevention of HIV infection. The major hypothesis to be tested is that strong virus specific CTL responses and neutralizing antibodies are associated with a delayed progression of HIV- 1 induced immune attrition. These studies will focus on a cohort of 164 patients with hemophilia, 73 percent of whom have been infected with HIV- 1 since 1981-83. In this cohort we have identified HIV-1 infected non- progressors, slow progressors and rapid progressors. Immunological and virological studies will be carried out on fresh and repository samples of sequential plasma and peripheral blood mononuclear collected prospectively during the course of the project. These investigators propose that HIV-specific cytotoxic T lymphocyte responses against a panel of HIV-1 proteins and neutralizing antibodies against autologous viral isolates. Viral isolates will be characterized for cytopathic Epstein Barr virus and measure CD4 T helper cell function to evaluate non-HIV directed defenses.